Pharmaceutical materials liquid solvent addition

Pyridine is a polar, stable, relatively unreactive liquid (bp 115°C) with a characteristic strong penetrating odor that is unpleasant to most people. It is miscible with both water and organic solvents. Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Pyridine can also be formed from the breakdown of many natural materials in the environment. 

The most efficient method of conducting SFE is via the dynamic process illustrated in Figure 15.4. This process enables the addition of a polar modifier such as methanol, which increases the solvent strength of the non-polar CO2. The liquid CO2 with about 5% v/v of modifier is passed though a stainless steel cell containing the sample, which may be mixed with inert material so that the sample occupies the whole cell volume. Two recent examples of the utilisation of SFE in the analysis of pharmaceuticals are discussed as follows. 

Levulinic acid is a highly reactive keto acid that is readily available from renewable materials. It has been proposed as a renewable basic chemical raw material (148-150) that can be used for a variety of purposes. These uses include plasticizers, pharmaceuticals, solvents, food additives, flavoring compounds, chemical intermediates, and resins and polymers. Recently, a-angelicalactone, which is formed on distillation of levulinic acid by the loss of a molecule of water, has been proposed as a liquid fuel extender (151),... 

Dimethyl ether may be used as a propellant and solvent in topical pharmaceutical aerosols, and is generally regarded as an essentially nontoxic and nonirritant material when used in such applications. However, inhalation of high concentrations of dimethyl ether vapor is harmful. Additionally, skin contact with dimethyl ether liquid may result in freezing of the skin and severe frostbite. 

Over the years a number of techniques and approaches have proved to be useful tools to successfully isolate low-level impiu ities and degradants. TLC is most useful when an impurity or degradant is identifiable by LC-MS and above the 1% level. In cases, where NMR analysis is essential for identification, semipreparative SFC, semipreparative HPLC, and flash chromatography are more suitable techniques. Please refer to the Handbook of Pharmaceutical Analysis, 1st ed. for a more in-depth explanation of TLC and flash chromatography s use for impurity isolation. As mentioned earlier, SPE and liquid-liquid extractions are at times incorporated into the process. These tools can quickly convert bulk supply materials into a more suitable form for SFC or HPLC injection. SPE is also a useful tool in dewatering and desalting final RP-HPLC isolated materials obtained from solvents containing mobile-phase additives. 

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